Nephron Patterning: Lessons from Xenopus, Zebrafish, and Mouse Studies

Abstract

The nephron is the basic structural and functional unit of the vertebrate kidney. To ensure kidney functions, the nephrons possess a highly segmental organization where each segment is specialized for the secretion and reabsorption of particular solutes. During embryogenesis, nephron progenitors undergo a mesenchymal-to-epithelial transition (MET) and acquire different segment-specific cell fates along the proximo-distal axis of the nephron. Even if the morphological changes occurring during nephrogenesis are characterized, the regulatory networks driving nephron segmentation are still poorly understood. Interestingly, several studies have shown that the pronephric nephrons in Xenopus and zebrafish are segmented in a similar fashion as the mouse metanephric nephrons. Here we review functional and molecular aspects of nephron segmentation with a particular interest on the signaling molecules and transcription factors recently implicated in kidney development in these three different vertebrate model organisms. A complete understanding of the mechanisms underlying nephrogenesis in different model organisms will provide novel insights on the etiology of several human renal diseases.

Keywords: metanephros; nephron segmentation; pronephros; regulatory networks; vertebrates.

Figure 1

Stages of kidney morphogenesis in Xenopus (A); zebrafish (B), and mouse (C). hpf: hours post-fertilization; IM: Intermediate Mesoderm; pro-: pronephros; meso-: mesonephros; meta-: metanephros; UB: Ureteric Bud; MM: Metanephric Mesenchyme; CM: Cap Mesenchyme; PA: Pretubular Agregate; RV: Renal Vesicle; CSB: Comma-Shaped-Body; SSB: S-Shaped-Body. IM, CM, and PA are shown in red, while renal epithelial tubular structures are in light blue.

Figure 2

Nephron segments and table of expression of marker genes. The different segments are depicted schematically with different colors showing the co-expression of selected markers in different segments in mature mouse/mammalian metanephric kidney (A), Xenopus pronephros (B), and zebrafish pronephros (C). Mature nephrons are observed from E16.5 in mouse, from 60 hpf in Xenopus pronephros and from 40 hpf in zebrafish. Segment names are abbreviated as follows: in mouse, G: glomerulus; N: neck; PS1, PS2, and PS3: segments of the proximal tubule, DTL: descending thin limb, ATL: ascending thin limb; TAL, thick ascending limb, MD: macula densa, DCT: distal convoluted tubule, CNT: connecting tubule; CD: collecting duct; in Xenopus, G: glomus; Ne: nephrostomes; PT1, PT2, and PT3: segments of proximal tubule; IT1 and IT2: segments of intermediate tubule; DT1 and DT2: segments of distal tubule; CT: collecting tubule; in zebrafish, G: glomerulus; N: neck; PCT: proximal convoluted tubule; PST: proximal straight tubule; DE: distal early; CS: Corpuscule of Stannius; DL: distal late; PD: pronephric duct. Yellow: glomerulus (in mouse and zebrafish) or glomus (in Xenopus); orange: neck (in mouse and zebrafish) or nephrostomes (in Xenopus); blue: proximal segments; green: intermediate segments; pink: distal segments; gray: duct. Half colored boxes indicate low expression.

Figure 3

Genetic pathways of nephron segmentation in Xenopus (A), zebrafish, (B) and mouse (C). Colors are the same as described in Figure 2.